Catheters are commonly utilized especially by physicians and other health care personnel for various purposes, such as the long and short term intravenous delivery (infusion) and withdrawal of fluids, such as nutrients, blood and blood products for treatment and monitoring of the patient. Examples of catheters include venous catheters, Swan-Ganz catheters, double and triple lumen central catheters, arterial catheters, arterial line monitoring catheters and foley bladder catheters, to name but a few.
Regardless of the type of catheter, each has in common the fact that, during use, they are at least partly inserted or otherwise disposed and maintained within a patient's body. For example, venous catheters are directly inserted into the vein of a patient. This is achieved by first properly aligning of the catheter with the target vein. Once properly aligned, the venous catheter is pushed (directly inserted) through the patient's skin, and into their vein. Other catheters such as closed suction drainage catheters and penrose drains are inserted into body wounds. Other catheters are inserted into body cavities such as the urinary tract (the foley bladder catheter), the aero-digestive tract (endotracheal tubes and tracheotomy tubes), nasal-gastric tubes, etc.
Two problems may arise when these catheters and medical devices are exposed to blood and/or body fluids. Droplets of the blood and/or body fluid remain on the catheter after its use and removal from the patient. If the patient is a carrier of a potentially infectious germs such as the human immunodeficiency virus (HIV) and the hepatitis B virus (HBV), the infection may be transmitted to other individuals who subsequently contact the contaminated catheter or medical device. If these individuals happen to have an abrasion in their own skin, they may become infected with these germs.
Two pathogenic germs that have been shown to be present in a potentially infective state in the blood and almost all the body fluids of infected patients are HIV and HBV. Because of the logarithmic increase in the number of people that carry either of these two viruses, a serious public health problem has arisen. Although the HIV is not capable of withstanding exposure to wide ranges of temperature and humidity changes, it is stable enough in the droplets of blood to remain viable and retain infectivity for more than three days if dried and held at room temperature, and for more than a week in an aqueous environment at room temperature. HBV is even more resistant and remains viable at room temperature for 6 months. Other germs that carry similar potential infectivity include hepatitis C, D and E, different bacteria, mycobacteria and fungi.
The enormous amount of medical waste generated by hospitals, clinics and laboratories must be disposed of in specially designed containers in order to avoid transmission of germs to health care providers. All health care professionals are required to observe the "Universal Blood and Body Fluid Precautions" developed by the Center for Disease Control in 1985. A study made by the Center for Disease Control established that the chances of health care workers acquiring HIV through accidental transmission from infected individuals is roughly one out of three hundred.
Another significant problem is that contaminated catheters and medical devices represent a potential hazard to the general public as well as to health care providers and to workers engaged in disposal of medically contaminated waste. The presence of HIV and other infectious germs on catheters and medical waste is a potential source of infection to anyone contacting these materials. Procedures for proper disposal have been instituted but the problem has not been eliminated. A need exists for a means to inhibit the infective gems on catheters and contaminated waste to protect the health of all persons who may contact these products subsequent to contamination by diseased patients.
Infection and inflammation is perhaps most commonly encountered at the point where the catheter is inserted through the skin (which normally forms a natural barrier against such infectants), as well as along the catheter's length. Such infection and inflammation can result in swelling of both of the limb, such as the patient's arm, and of the vein itself. If the catheter is in body cavities, such as the bladder, ear or aero-digestive tract, infection and inflammation of these cavities may occur with formation of granulation tissue and blockage of these cavities. However, and more seriously, bacteria/fungi can also migrate into the patient's bloodstream or body organs resulting in bacteremia/fungemia or infection of the bloodstream, thereby spreading the infection throughout the patient's body. Such a condition can often be fatal, especially if the infection spreads to the patient's heart or other organs.
Further, if the catheter is positioned within the patient's body for a prolonged period of time, tissue growth (for example, granulation or fibrosis) may develop about the catheter, as a natural consequence of the body's natural defense mechanisms against the presence of the contaminant. Such tissue growth can be harmful to the patient by, for example, "adhering" the catheter to the vein. This condition can complicate removal of the catheter by causing the vein to be torn and ruptured when the catheter is removed, resulting in internal bleeding.
To compound the above-mentioned problems of infection, inflammation and tissue growth, often the only method of treating such problems is by the systemic administration of antibiotics, etc. Unfortunately, such systemic treatments can be costly, and can result in change of bacterial flora and emergence of resistance. Such systemic treatments can also decrease healing and have other undesirable side effects.
All-in-all, as can be readily understood, the above-mentioned problems of infection and inflammation represent grave problems of longstanding duration. These problems have curtailed the use of catheters, so that standard catheters can be utilized only for several days at a time before they must be removed and a new one inserted. Such a situation creates a further problem in that the insertion and removal of catheters (especially where central venous catheters are involved) can be a dangerous task.
Thus, the use of catheters presents potential problems to the environment of health care providers who must handle catheters which have been exposed to blood and other body fluids of patients, and also to the patient in whom the catheter is implanted who may become infected from germs on the catheter or introduced into the cavity in which the catheter is implanted.
It has been proposed to fight bacterial infection by incorporating and/or binding antibiotics and antimicrobial agents into various medical devices (such as catheters, bandages, implants, ocular inserts and interuterine devices) which are inserted into a patient's body. Once inserted, these antibiotic/antimicrobial agents are released or leeched therefrom for preventing infection. Examples of such devices are the catheters disclosed in U.S. Pat. Nos. 3,598,127 issued to Wepsic (a urinary tract catheter of nonpermeable rubber in which antibiotics, such as neomycin is infused); 4,186,745 (wherein antibacterial substances are infused into microporous polyethylene, polypropylene or polyfluorocarbon polymers); 4,054,139 issued to Crossley (wherein oligodynamic agents, such as metallic silver and other heavy metals are incorporated onto catheter surfaces); and 3,566,874 issued to Shepard (wherein antibiotics and germicides, such as penicillin and cetylpyridinium chloride are infused into a hydrophilic polymer for coating medical appliances). Other examples are disclosed in U.S. Pat. Nos. 4,603,152 issued to Lavrin; 4,642,104 issued to Sakamoto et al; 4,650,488 issued to Bays et al; 4,879,135 issued to Greco et al; 4,950,256 issued to Luthoer et al; 5,013,306 issued to Solomon et al; 5,028,597 issued to Kodama et al; 5,019,096 issued to Fox, Jr. et al; and 5,019,601 issued to Allen.
While being generally useful, in varying degrees, for their intended purposes of fighting infection on a localized level, each of these approaches suffers from one or more of the following disadvantages: (1) they merely involve mixtures and the antibacterial agent is neither chemically combined to the plastic nor slowly released; (2) the antibiotic/antimicrobial substances proposed are effective only against specific bacteria and not against aggressive microbes such as viruses (e.g., HIV and hepatitis); and (3) those disclosures involving bioerodible coatings present the undesirable side effect of also releasing the bioerodible coating into the patient's body with all of the attendant problems that that presents.
The use of a multi-layer cannula which is swellable and controls the rate of water passage through the layers and controls the diffusion of medicaments is disclosed in U.S. Pat. No. 4,994,047 issued to Walker et al.
Commonly-utilized and well-accepted for inhibiting infection is the use of iodine. Iodine is a broad spectrum antimicrobial agent that has bactericidal, fungicidal and viricidal properties. When iodine reacts with aqueous solutions, free iodine, which provides the germicidal effect, is released. While generally inhibiting infective germs over the short term, the biocidal effectiveness of iodine is dependent on, inter alia, how long the contaminant is exposed to it. This is particularly important in the case of HIV and HBV where the iodine is effective only after it remains in contact with the virus for a relatively long period of time (more than 10 minutes). Thus, over the long term, since topically applied iodine is released all at once, it does not provide adequate sustained protection. Further, such topical application is of little to no use in inhibiting internal infection either in the short term or in the long term.
To increase the effectiveness of iodine, it is normally incorporated into solutions, soaps, creams, pastes, etc., to form an iodophor. Such iodophors, in effect, provide a reservoir of iodine from which small amounts of free iodine in aqueous solution are released over a period of time. These iodophors are then topically applied to that area of a patient's body which is desired to be treated. Perhaps the best known of these iodophors is povidone-iodine, a compound of polyvinylpyrrolidone with iodine. An example of such an application can be found by reference to U.S. Pat. No. 4,010,259 issued to Johansson.
It has been disclosed to incorporate iodophors onto various medical paraphernalia for topical application. In U.S. Pat. Nos. 3,235,446 issued to Shelanski et al, iodinated polyurethane foams and films are incorporated into bandages and sponges. Similarly, U.S. Pat. No. 3,401,005 issued to Katz discloses fibrous materials (such as gauze) that are treated with combinations of polymers, halogens and iodine for use in bandages and surgical dressings. U.S. Pat. No. 4,094,967 issued to Gilbert discloses compositions method of binding iodine to polyvinylpyrrolidone with the use of cinnamic alcohol or tannic acid which is to be applied to matting, gauzes and foam rubber for topical use. U.S. Pat. No. 4,113,851 issued to Le Veen et al, discloses a composition of iodine, pyrrolidone polymer and a polymeric basic acid for incorporation into salve-ointments, dressings or bandages. U.S. Pat. No. 5,156,164 issued to Le Veen et al discloses a contraceptive sponge consisting of a polyurethane open cell foam impregnated with surfactant and iodine.
While being useful for their various purposes of generally inhibiting bacterial infection at the point of the insertion over the short term, all of those references disclose compositions into which the iodine has been complexed for topical application only.
U.S. Pat. No. 5,071,648 issued to Rosenblatt discloses films and sponges formed from polyvinyl alcohol complexed with iodine, which provides a controlled release of iodine.
It has also been disclosed in U.S. Pat. No. 4,381,380 issued to Le Veen et al, to provide cross-linked thermoplastic polyurethane articles, such as catheters, into which iodine has been complexed for antibacterial use. While being useful for their purpose, such cross-linked thermoplastics cannot be utilized for coatings.
As is well-known, polymers, such as polyurethanes, may be either essentially cross-linked or essentially uncross-linked. The uncross-linked polymers are suitable for the production of coatings, but are not of a tensile strength which is acceptable to fashion appliances, such as catheters, which require more exacting physical properties. The cross-linked polymers are suitable for the production of appliances, but are not suitable for the production of coatings, such as the ones noted herein. Further, cross-linked polymers possess a steric hinderance that renders inaccessible many, and sometimes all, of the linkages which complex with the iodine.
It would be extremely advantageous to provide a catheter which has a thermoset uncross-linked polymer coating that has iodine either complexed therein for quick and relative immediate release of the iodine and/or matrixed therein for sustained release of the iodine.
Thus, it can be seen that there remains a need for catheters that are solvent coatable with a polymeric dispersion or solution that have iodine complexed and/or matrixed therein, so as to provide for immediate and/or sustained release of the iodine therefrom for inhibiting infection, that is commonly associated with the use of such catheters.